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Background: The COVID-19 pandemic significantly threatens immunocompromised patients. We aimed to investigate the clinical and paraclinical findings and consequences of COVID-19 in kidney transplantation recipients. Methods: In this retrospective study, kidney transplant recipients admitted to Ayatollah Rouhani, Shahid Beheshti, and Shahid Yahyanejad referral hospitals of Babol, North of Iran, with a diagnosis of COVID-19, were examined. Information such as demographic and laboratory findings, clinical symptoms, and treatments received was entered into pre-prepared questionnaires. Results: Out of the 35 patients included in the study, 19 (54.3%) were males, and 16 (45.7%) were females. The mean age of patients was 47.46±11.28. Among the clinical symptoms, cough and decreased level of consciousness were associated with a higher mortality rate (P= 0.02). Furthermore, the mortality rate was found to be 17.1%. Creactive protein (CRP) level, oxygen saturation percentage, and diffuse lung involvement were significantly associated with COVID-19 mortality (p <0.05). In this study, no correlation was found between the amount of Cr and the outcome of COVID- 19 disease (P = 0.66), and also, no significant relationship was found between the amount of BUN and the outcome of COVID-19 (P = 0.46). Even the patient who was admitted with a Cr of 6.4 did not die and was discharged with a Cr of 3.4. Conclusion: Due to the higher mortality rate in transplant patients with COVID-19, the need for more clinically severe treatment and intensification of care in this group of patients is essential. [ABSTRACT FROM AUTHOR]

Background and Purpose: There is a need for effective anti‐COVID‐19 treatments, mainly for individuals at risk of severe disease such as the elderly and the immunosuppressed. Drug repositioning has proved effective in identifying drugs that can find a new application for the control of coronavirus disease, in particular COVID‐19. The purpose of the present study was to find synergistic antiviral combinations for COVID‐19 based on lethal mutagenesis. Experimental Approach: The effect of combinations of remdesivir and ribavirin on the infectivity of SARS‐CoV‐2 in cell culture has been tested. Viral populations were monitored by ultra‐deep sequencing, and the decrease of infectivity as a result of the treatment was measured. Key Results: Remdesivir and ribavirin exerted a synergistic inhibitory activity against SARS‐CoV‐2, quantified both by CompuSyn (Chou‐Talalay method) and Synergy Finder (ZIP‐score model). In serial passage experiments, virus extinction was readily achieved with remdesivir‐ribavirin combinations at concentrations well below their cytotoxic 50 value, but not with the drugs used individually. Deep sequencing of treated viral populations showed that remdesivir, ribavirin, and their combinations evoked significant increases of the number of viral mutations and haplotypes, as well as modification of diversity indices that characterize viral quasi‐species. Conclusion and Implications: SARS‐CoV‐2 extinction can be achieved by synergistic combination treatments based on lethal mutagenesis. In addition, the results offer prospects of triple drug treatments for effective SARS‐CoV‐2 suppression. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a severe respiratory disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that affects the lower and upper respiratory tract in humans. SARS-CoV-2 infection is associated with the induction of a cascade of uncontrolled inflammatory responses in the host, ultimately leading to hyperinflammation or cytokine storm. Indeed, cytokine storm is a hallmark of SARS-CoV-2 immunopathogenesis, directly related to the severity of the disease and mortality in COVID-19 patients. Considering the lack of any definitive treatment for COVID-19, targeting key inflammatory factors to regulate the inflammatory response in COVID-19 patients could be a fundamental step to developing effective therapeutic strategies against SARS-CoV-2 infection. Currently, in addition to well-defined metabolic actions, especially lipid metabolism and glucose utilization, there is growing evidence of a central role of the ligand-dependent nuclear receptors and peroxisome proliferatoractivated receptors (PPARs) including PPARα, PPARβ/δ, and PPARγ in the control of inflammatory signals in various human inflammatory diseases. This makes them attractive targets for developing therapeutic approaches to control/suppress the hyperinflammatory response in patients with severe COVID-19. In this review, we (1) investigate the anti-inflammatory mechanisms mediated by PPARs and their ligands during SARS-CoV-2 infection, and (2) on the basis of the recent literature, highlight the importance of PPAR subtypes for the development of promising therapeutic approaches against the cytokine storm in severe COVID-19 patients. [ABSTRACT FROM AUTHOR]

The need for new coronavirus disease 2019 (COVID-19) therapeutic strategies continues, especially as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants emerge. Zhang and colleagues elegantly engineered a mutant angiotensin-converting enzyme 2 (ACE2) that competitively binds SARS-CoV-2 spike protein, reduces viral uptake by human lung cells, and ameliorates SARS-CoV-2-induced lung injury in mice expressing human ACE2.

In the effort to combat SARS-CoV-2 infection, researchers are currently exploring the repurposing of conventional antiviral drugs, despite their limited efficacy. The SARS-CoV-2 virus encodes a papain-like protease (PLpro), which not only plays a crucial role in viral replication but also cleaves ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host proteins, making it a prime target for the development of new antiviral medications. In this study, we conducted a multi-step in silico screening to identify novel, noncovalent PLpro inhibitors. Curcumin, an antioxidant derived from turmeric rhizomes (Curcuma longa L.), has undergone extensive preclinical investigations and shown significant efficacy against viruses and other ailments in both laboratory and animal studies. However, the pharmacological limitations of curcumin have prompted the synthesis of numerous novel curcumin analogs, necessitating evaluation for their therapeutic potential. The selectivity of the top-scoring compounds was assessed through molecular docking studies and molecular dynamics simulations to determine their binding affinity to PLpro. As a result, we identified 20 potential, selective PLpro inhibitors, from which the top two compounds (THA111 and THHGV6) were selected based on their binding free energy values towards PLpro as estimated by MM-PBSA calculations. These selected candidates demonstrate promising activity against the protein, with binding free energy values ranging from approximately -105 to -108 kJ/mol, and largely adopt a similar binding mode to known noncovalent SARS-CoV-2 PLpro inhibitors (GRL0617 = -100.98 kJ/mol). We further propose these two most promising compounds for future in vitro evaluation. The findings for the top potential PLpro inhibitors have been deposited in a database (Curcumin Research Center) to aid research on anti-SARS-CoV-2 drugs. [ABSTRACT FROM AUTHOR]

This article reviews studies on SARS-CoV-2 antibodies, including neutralizing antibodies (NAbs) and post-vaccination response. The SARS-CoV-2 virus is closely related to SARS-CoV and MERS-CoV, sharing 79% and 50% of its genome sequence with them, respectively. Antibodies are crucial in identifying and destroying pathogens such as viruses, and understanding virus-specific antibodies can help end pandemics quickly. The SARS-CoV-2 virus uses the spike protein to enter human cells via the angiotensin-converting enzyme 2 receptor (ACE2). The immune response to the virus involves various components, including dendritic cells, T cells, B cells, and NAbs. Seroconversion, antibody kinetics, and immune response after COVID-19 vaccination are essential factors in understanding the virus and developing treatments. Neutralizing antibody therapies have been explored as potential treatments, but the emergence of viral variants challenges their long-term development. Lessons learned from antibody-based therapies can influence future strategies for treating emerging infectious diseases.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly infectious positive RNA virus, has spread from its epicenter to other countries with increased mortality and morbidity. Its expansion has hampered humankind's social, economic, and health realms to a large extent. Globally, investigations are underway to understand the complex pathophysiology of coronavirus disease (COVID-19) induced by SARS-CoV-2. Though numerous therapeutic strategies have been introduced to combat COVID-19, none are fully proven or comprehensive, as several key issues and challenges remain unresolved. At present, natural products have gained significant momentum in treating metabolic disorders. Mushrooms have often proved to be the precursor of various therapeutic molecules or drug prototypes. The plentiful bioactive macromolecules in edible mushrooms, like polysaccharides, proteins, and other secondary metabolites (such as flavonoids, polyphenols, etc.), have been used to treat multiple diseases, including viral infections, by traditional healers and the medical fraternity. Some edible mushrooms with a high proportion of therapeutic molecules are known as medicinal mushrooms. In this review, an attempt has been made to highlight the exploration of bioactive molecules in mushrooms to combat the various pathophysiological complications of COVID-19. This review presents an in-depth and critical analysis of the current therapies against COVID-19 versus the potential of natural anti-infective, antiviral, anti-inflammatory, and antithrombotic products derived from a wide range of easily sourced mushrooms and their bioactive molecules. [ABSTRACT FROM AUTHOR]

This article reviews studies on SARS-CoV-2 antibodies, including neutralizing antibodies (NAbs) and post-vaccination response. The SARS-CoV-2 virus is closely related to SARS-CoV and MERS-CoV, sharing 79% and 50% of its genome sequence with them, respectively. Antibodies are crucial in identifying and destroying pathogens such as viruses, and understanding virus-specific antibodies can help end pandemics quickly. The SARS-CoV-2 virus uses the spike protein to enter human cells via the angiotensin-converting enzyme 2 receptor (ACE2). The immune response to the virus involves various components, including dendritic cells, T cells, B cells, and NAbs. Seroconversion, antibody kinetics, and immune response after COVID-19 vaccination are essential factors in understanding the virus and developing treatments. Neutralizing antibody therapies have been explored as potential treatments, but the emergence of viral variants challenges their long-term development. Lessons learned from antibody-based therapies can influence future strategies for treating emerging infectious diseases. [ABSTRACT FROM AUTHOR]

While the COVID-19 pandemic seems to be on its decline, the unclear impacts of long-COVID cases, breakthrough infections in immunocompromised individuals, vaccine hesitancy, and inhomogeneous health-care accessibility constitute a not to be underestimated threat. These cases, along with pandemic preparedness, ask for an alert identification of new drugs and the optimization of existing drugs as therapeutic treatment options for this and potential future diseases. Mpro inhibitors were identified early on as potent drug candidates against coronaviruses, since they target viable processing machinery within the virus, i.e., the main protease that cleaves the polyproteins encoded by the viral RNA into functional proteins. Different strategies, including reversible and irreversible inhibition as well as allosteric inhibitors, mostly from drug repurposing endeavors, have been explored in the design of potent SARS-CoV-2 Mpro antivirals. Ambitious screening efforts have uttered an outstanding chemical and structural diversity, which has led to half a dozen lead compounds being currently in clinical trials and the emergency FDA approval of ritonavir-boosted nirmatrelvir as a COVID-19 therapeutic. This comprehensive analysis of the achieved inhibitor diversity sorted into irreversible, reversible, and allosteric Mpro binders, along with a discussion of emerging resistance reports and possible evasion strategies, is aimed at stimulating continuing Mpro drug design efforts.

The recent outbreak of corona virus and coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus is a global concern. Despite efforts to clarify the physiology and potential therapy, specific guidelines for the treatment of COVID-19 disease have yet to be established, and many therapeutic options are under investigation. Accumulating evidence suggests that dysregulation of iron homeostasis contributes significantly to the pathogenesis of COVID-19 through its toxic effects by the formation of reactive oxygen species (ROS). This review focuses on summarizing the available literature and relevant studies conducted to date on the possible therapeutic effects of iron chelation therapy in the treatment of COVID-19 disease. Scientific databases (PubMed, Scopus, Google Scholar) were searched for relevant articles using the following keywords: COVID-19, SARS-CoV-2, coronavirus, clinical management, iron chelators/chelation. Research articles, reviews, research letters, case reports, and commentaries were considered. Although there is ample evidence of the potential beneficial effects of using iron chelators as adjuvant treatment in COVID-19, further research on this topic is needed.

Abstract Background The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies. Methods To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle. Results 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57–73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61–2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63–2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively. Conclusions Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020

Introduction: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. Methods: All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 were retrospectively enrolled. The primary outcome was the progression to severe COVID-19 (P/F < 200). Descriptive statistics, a Cox univariate–multivariate model, and an inverse probability treatment-weighted (IPTW) analysis were performed. Results: Overall, 331 subjects were included; their median (q1–q3) age was 71 (51–80) years, and they were males in 52% of the cases. Of them, 78 (23%) developed severe COVID-19. All-cause in-hospital mortality was 14%; it was higher in those with disease progression (36% vs. 7%, p < 0.001). REM and mAbs resulted in a 7% (95%CI = 3–11%) and 14% (95%CI = 3–25%) reduction in the risk of severe COVID-19, respectively, after adjusting the analysis with the IPTW. In addition, by evaluating only immunocompromised hosts, the combination of REM and mAbs was associated with a significantly lower incidence of severe COVID-19 (aHR = 0.06, 95%CI = 0.02–0.77) when compared with monotherapy. Conclusions: REM and mAbs may reduce the risk of COVID-19 progression in hospitalized patients. Importantly, in immunocompromised hosts, the combination of mAbs and REM may be beneficial. [ABSTRACT FROM AUTHOR]

While the COVID-19 pandemic seems to be on its decline, the unclear impacts of long-COVID cases, breakthrough infections in immunocompromised individuals, vaccine hesitancy, and inhomogeneous health-care accessibility constitute a not to be underestimated threat. These cases, along with pandemic preparedness, ask for an alert identification of new drugs and the optimization of existing drugs as therapeutic treatment options for this and potential future diseases. Mpro inhibitors were identified early on as potent drug candidates against coronaviruses, since they target viable processing machinery within the virus, i.e., the main protease that cleaves the polyproteins encoded by the viral RNA into functional proteins. Different strategies, including reversible and irreversible inhibition as well as allosteric inhibitors, mostly from drug repurposing endeavors, have been explored in the design of potent SARS-CoV-2 Mpro antivirals. Ambitious screening efforts have uttered an outstanding chemical and structural diversity, which has led to half a dozen lead compounds being currently in clinical trials and the emergency FDA approval of ritonavir-boosted nirmatrelvir as a COVID-19 therapeutic. This comprehensive analysis of the achieved inhibitor diversity sorted into irreversible, reversible, and allosteric Mpro binders, along with a discussion of emerging resistance reports and possible evasion strategies, is aimed at stimulating continuing Mpro drug design efforts. [ABSTRACT FROM AUTHOR]

Background and Aim: Previous studies have shown that viral and host miRNAs play a role in the process of controlling or progressing the disease and can even be considered as therapeutic targets. Accordingly, the present review study was designed to evaluate the role of host miRNAs and Covid-19 virus in the disease process. Materials and Methods: The current study was a review study that was conducted during 2012-2022. Studies were extracted from PubMed, Google Scholar, Web of Science and Scopus scientific databases. The researchers selected relevant resources and a summary of them was presented in this review. Results: The present review study showed that some host miRNAs such as miR-23b-5p, miR-200c, and miR-125a-5p had an inhibitory effect on ACE2 receptor, while miR-3909, miR-4677, and miR-133a had a stimulatory effect on this receptor. Furthermore, host miR-98-5p had an inhibitory effect on TMPRSS2 gene expression. On the other hand, host miR-146a, miR-21, and miR-142 induced inflammation through MAPK and NF-Ƙβ signaling. While, host miR-124, miR-410, and miR-1336 inhibited factor STAT3 and prevented inflammation. Furthermore, host miR-302b and miR-372 targeted the mitochondrial antiviral signaling protein (MAVS), resulting in silencing of type 1 interferon signaling. It has also been established that host exosomal miR-7-5p, miR-24-3p, miR-145-5p, and miR-223-3p inhibited the replication of SARS-CoV-2 and the expression of S protein and their decreased expression in elderly and Diabetic subjects was associated with decreased inhibition of SARS-CoV-2 replication. Moreover, viral miR-359-5p regulated the expression of MYH9 (non-muscle myosin heavy chain 9), which caused virus invasion and release in the host cell. Conclusion: This study showed that many miRNAs play a role in controlling or progressing the disease of Covid-19 and it is possible to treat the disease of Covid-19 by changing the expression of viral and host miRNA. However, more research is needed in this regard.

The emergence of issues regarding the drug dexamethasone as a prevention of Coronavirus Disease 2019 (COVID-19) has made the public look for dexamethasone without exploring the further information. Inappropriate use of dexamethasone drugs can cause side effects such as reduced immunity. This study aims to determine the profile of public knowledge in East Java regarding the function, side effects, and usage of dexamethasone as a therapeutic treatment for COVID-19 patients. This study is a cross-sectional study by collecting data using non-random sampling techniques (accidental sampling) and the research instrument using an online questionnaire. Based on the results of this study, 237 respondents were obtained with characteristics of the gender consisting of 78.9% women and 21.1% men and the ages of 18-23 years (88.61%), 24-28 years (3.66%), and >28 years (7.79%). The results showed that 1.69% of respondents had low knowledge, 54.85% of respondents had moderate knowledge, and 43.46% of respondents had high knowledge regarding the functions, side effects, and use of dexamethasone as a therapeutic treatment for COVID-19 patients. According to the results of this study, it is necessary to increase public knowledge in East Java regarding the functions, side effects, and use of dexamethasone as a therapeutic treatment for COVID-19 patients to prevent misperceptions on the use of dexamethasone as a therapeutic treatment for COVID-19 patients. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a severe respiratory disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that affects the lower and upper respiratory tract in humans. SARS-CoV-2 infection is associated with the induction of a cascade of uncontrolled inflammatory responses in the host, ultimately leading to hyperinflammation or cytokine storm. Indeed, cytokine storm is a hallmark of SARS-CoV-2 immunopathogenesis, directly related to the severity of the disease and mortality in COVID-19 patients. Considering the lack of any definitive treatment for COVID-19, targeting key inflammatory factors to regulate the inflammatory response in COVID-19 patients could be a fundamental step to developing effective therapeutic strategies against SARS-CoV-2 infection. Currently, in addition to well-defined metabolic actions, especially lipid metabolism and glucose utilization, there is growing evidence of a central role of the ligand-dependent nuclear receptors and peroxisome proliferator-activated receptors (PPARs) including PPARα, PPARβ/δ, and PPARγ in the control of inflammatory signals in various human inflammatory diseases. This makes them attractive targets for developing therapeutic approaches to control/suppress the hyperinflammatory response in patients with severe COVID-19. In this review, we (1) investigate the anti-inflammatory mechanisms mediated by PPARs and their ligands during SARS-CoV-2 infection, and (2) on the basis of the recent literature, highlight the importance of PPAR subtypes for the development of promising therapeutic approaches against the cytokine storm in severe COVID-19 patients.

Background: The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies.Methods: To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle.Results: 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57-73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively.Conclusions: Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020. [ABSTRACT FROM AUTHOR]

Background: Polymyxin B-immobilized fiber column (PMX; Toraymyxin column) was approved for the relief of systemic inflammatory response syndrome caused by bacterial infection or endotoxemia. PMX reduces lung damage by removing leukocytes and cytokines in addition to endotoxin removal in the setting of idiopathic pulmonary fibrosis. Acute exacerbation of interstitial pneumonia pathologically presents with diffuse alveolar damage (DAD). PMX direct hemoperfusion (PMX-DHP) demonstrated efficacy, improving oxygenation. The SARS-CoV-2 virus causes COVID-19, which emerged in December 2019. The condition may become severe about 1 week after onset, and respiratory failure rapidly develops, requiring intensive care management. A characteristic of COVID-19-related severe pneumonia is ground-glass opacities rapidly progressing in both lungs, which subsequently turn into infiltrative shadows. This condition could be classified as DAD. As for the congealing fibrinogenolysis system, D-dimer, fibrin/fibrinogen degradation product quantity, and prolonged prothrombin time were significant factors in nonsurviving COVID-19 cases, associated with aggravated pneumonia. Clinical trials are being conducted, but except for remdesivir and dexamethasone, no treatments have yet been approved. COVID-19 aggravates with the deterioration of oxygen saturation, decrease in lymphocytes, and the occurrence of an abnormal congealing fibrinogenolysis system, leading to diffuse lung damage. Once the condition transitions from moderate to severe, it is necessary to prevent further exacerbation by providing treatment that will suppress the aforementioned symptoms as soon as possible. Objective: This study aims to access treatment options to prevent the transition from acute exacerbation of interstitial pneumonia to DAD. The mechanism of action envisioned for PMX-DHP is to reduce congealing fibrinogenolysis system abnormalities and increase oxygenation by removing activated leukocytes and cytokines, which are risk factors for the aggravation of COVID-19-related pneumonia. Methods: We will conduct a multicenter, prospective, intervention, single-group study to evaluate the efficacy and safety of direct hemoperfusion using PMX-DHP for patients with COVID-19. Efficacy will be evaluated by the primary end point, which is the rate of Ordinal Scale for Clinical Improvement after PMX-DHP of at least 1 point from a status of 4, 5, or 6 on day 15. The effect of PMX-DHP will be estimated by setting a control group with background factors from non-PMX-DHP patients enrolled in the COVID-19 registry. This study will be carried out as a single-group open-label study and will be compared with a historical control. The historical control will be selected from the COVID-19 registry according to age, gender, and severity of pneumonia. Results: The study period is scheduled from September 28, 2020, through April 30, 2023. Patient enrollment was scheduled from the Japan Registry of Clinical Trials publication for March 31, 2022. Data fixation is scheduled for October 2022, with the publication of the results by March 2023. Conclusions: From a clinical perspective, PMX-DHP is expected to become an adjunctive therapy to address unmet medical needs and prevent the exacerbation from moderate to severe acute respiratory distress syndrome in COVID-19 cases. [ABSTRACT FROM AUTHOR]

Background: Remdesivir, an RNA-polymerase prodrug inhibitor approved for treatment of coronavirus disease 2019 (COVID-19), shortens recovery time and improves clinical outcomes. This prespecified analysis compared remdesivir plus standard of care (SOC) with SOC alone in adults hospitalized with COVID-19 requiring oxygen support in the early stage of the pandemic., Methods: Data for 10-day remdesivir treatment plus SOC from the extension phase of an open-label study (NCT04292899) were compared with real-world, retrospective data on SOC alone (EUPAS34303). Both studies included patients aged ≥18 years hospitalized with severe acute respiratory syndrome coronavirus 2 up to 30 May 2020, with oxygen saturation ≤94% on room air or supplemental oxygen (all forms), and with pulmonary infiltrates. Propensity score weighting was used to balance patient demographics and clinical characteristics across treatment groups. The primary endpoint was time to all-cause mortality or end of study (day 28). Time to discharge, with a 10-day landmark to account for duration of remdesivir treatment, was a secondary endpoint., Results: A total of 1974 patients treated with remdesivir plus SOC, and 1426 with SOC alone, were included after weighting. Remdesivir significantly reduced mortality versus SOC (hazard ratio [HR], 0.46; 95% confidence interval, .39-.54). This association was observed at each oxygen support level, with the lowest HR for patients on low-flow oxygen. Remdesivir significantly increased the likelihood of discharge at day 28 versus SOC in the 10-day landmark analysis (HR, 1.64; 95% confidence interval: 1.43-1.87)., Conclusions: Remdesivir plus early-2020 SOC was associated with a 54% lower mortality risk and shorter hospital stays compared with SOC alone in patients hospitalized with COVID-19 requiring oxygen support. Clinical Trials Registration.  ClinicalTrials.gov NCT04292899 and EUPAS34303., Competing Interests: Potential conflicts of interest. D. F. has served on advisory boards for Gilead Sciences, Inc. and Axcella, and as site principal investigator for clinical trials sponsored by Gilead Sciences, Inc., MetroBiotech, LLC, the National Institutes of Health (NIH; DMID COVAIL), and Regeneron. H. F. G. has received honoraria as a member of DMC or advisory boards for Gilead Sciences, Inc., GSK, Janssen, Johnson and Johnson, Merck, Novartis, and ViiV Healthcare. Furthermore, he has received grants outside of this work from the NIH, Swiss HIV Cohort Study, Swiss National Science Foundation, and Yvonne Jacob Foundation; and has received unrestricted research grants from Gilead Sciences, Inc. All grants were paid to his institution. He has also received a travel grant from Gilead Sciences, Inc. for conference attendance. S. K. G. has received independent grant funding from Indiana University, the NIH, and ViiV Healthcare; and has received consulting/advisory fees from Gilead Sciences, Inc. and ViiV Healthcare. D. K. has received consulting fees from E.R. Squibb & Sons, LLC, and holds stock options in HCA Healthcare. B. B. has received grants from AstraZeneca, Gilead Sciences, Inc., and NIH; has received consulting fees, speaker honoraria, and travel support from Gilead Sciences, Inc.; has participated on a Data Safety Monitoring Board (DSMB) or advisory board for Gilead Sciences, Inc. and is a Gilead Sciences, Inc. speaker for their hepatitis C virus antiviral agent. S. O. has received research funding from HRSA Ryan White Funds. J. A. A. has received institutional research support for clinical trials from Emergent BioSolutions, Frontier Technologies, Gilead Sciences, Inc., GSK, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare; has received personal fees for advisory boards from GSK/ViiV Healthcare and Merck; and has participated on a DSMB for Kintor Pharmaceutical, all outside the submitted work. I. M., L. E. T., Y. T., C. B., G. W., R. H., C.-Y. W., A. P. C., and A. O. O. are employees of, and stockholders in, Gilead Sciences, Inc. C.-M. W. has received research funding and travel grants from Gilead Sciences, Inc. for this study; has received research grants or contracts; consulting fees, payment, or honoraria for lectures, presentations, or educational events; and travel support from AbbVie, AstraZeneca, BeiGene, BioNTech, Hoffmann-La Roche, Janssen, and Moderna; and has participated on a Data DSMB or advisory board for AbbVie, AstraZeneca, BeiGene, BioNTech, Hoffmann-La Roche, Janssen, and Moderna. R. L. G. has received grants or contracts to his institution from Eli Lilly, Gilead Sciences, Inc., Johnson & Johnson, Pfizer, Regeneron, and Roivant Sciences (Kinevant Sciences); has received consulting fees from AbbVie, Eli Lilly, Gilead Sciences, Inc., GSK, and Roche; has received payment or honoraria for lectures/speaker fees from Gilead Sciences, Inc. and Pfizer (for an unrelated field); has received travel support from Gilead Sciences, Inc.; has participated on advisory boards for AbbVie, AstraZeneca, Eli Lilly, Gilead Sciences, Inc., GSK, Johnson & Johnson, Kinevant Sciences, and Roche/Genentech; is a de minimis stockholder at AbCellera; and received a gift-in-kind to his institution for an unrelated clinical trial (NCT03383419) from Gilead Sciences, Inc. during the conduct of this study. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. 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Around four years have passed since the globe was shaken by the COVID-19 pandemic, triggered by SARS-CoV-2, affecting almost one billion individuals worldwide and claiming the lives of millions. Despite stringent safety measures and the swift expansion of vaccination initiatives, managing waves of illness has proven challenging. Given its crucial involvement in replication and notable conservation, our team persisted in focusing on the SARS-CoV-2 main protease enzyme (Mpro) as a highly promising therapeutic objective. Accordingly, a multistep computer-aided drug discovery process was used in this study to elucidate potential lead candidates targeting SARS-CoV-2 Mpro. A protein-ligand interaction fingerprint (PLIF) tool was utilized to help design a structure-based pharmacophore based on critical interactions between known ligands and the Mpro active site. The produced pharmacophore was used to filter a fraction of the ZINC database of chemical substances, resulting in 703 possible hits. All the filtered compounds achieved acceptable docking scores and four compounds achieved higher docking scores of selected Mpro inhibitor reference, and the top-ranked compound W1 (ZINC000150656136) was selected for more simulations. A combination of traditional molecular dynamics (MD) and MM-PBSA was used in the final step. W1 has been predicted to engage with multiple essential interactions with key residues in the Mpro active with a docking score and binding free energy of 11.1 kcal/mol and -324.7 ± 9.7 Kj/mol, respectively. As a result, we propose W1 as a lead compound candidate towards the SARS-CoV-2 Mpro enzyme that can be forwarded for experimental validation and clinical studies for COVID-19 management.

Background: During the pandemic, health care providers implemented remote patient monitoring (RPM) for patients experiencing COVID-19. RPM is an interaction between health care professionals and patients who are in different locations, in which certain patient functioning parameters are assessed and followed up for a certain duration of time. The implementation of RPM in these patients aimed to reduce the strain on hospitals and primary care., Objective: With this literature review, we aim to describe the characteristics of RPM interventions, report on patients with COVID-19 receiving RPM, and provide an overview of outcome variables such as length of stay (LOS), hospital readmission, and mortality., Methods: A combination of different searches in several database types (traditional databases, trial registers, daily [Google] searches, and daily PubMed alerts) was run daily from March 2020 to December 2021. A search update for randomized controlled trials (RCTs) was performed in April 2022., Results: The initial search yielded more than 4448 articles (not including daily searches). After deduplication and assessment for eligibility, 241 articles were retained describing 164 telemonitoring studies from 160 centers. None of the 164 studies covering 248,431 patients reported on the presence of a randomized control group. Studies described a "prehosp" group (96 studies) with patients who had a suspected or confirmed COVID-19 diagnosis and who were not hospitalized but closely monitored at home or a "posthosp" group (32 studies) with patients who were monitored at home after hospitalization for COVID-19. Moreover, 34 studies described both groups, and in 2 studies, the description was unclear. In the prehosp and posthosp groups, there were large variations in the number of emergency department (ED) visits (0%-36% and 0%-16%, respectively) and no convincing evidence that RPM leads to less or more ED visits or hospital readmissions (0%-30% and 0%-22%, respectively). Mortality was generally low, and there was weak to no evidence that RPM is associated with lower mortality. Moreover, there was no evidence that RPM shortens previous LOS. A literature update identified 3 small-scale RCTs, which could not demonstrate statistically significant differences in these outcomes. Most papers claimed savings; however, the scientific base for these claims was doubtful. The overall patient experiences with RPM were positive, as patients felt more reassured, although many patients declined RPM for several reasons (eg, technological embarrassment, digital literacy)., Conclusions: Based on these results, there is no convincing evidence that RPM in COVID-19 patients avoids ED visits or hospital readmissions and shortens LOS or reduces mortality. On the other hand, there is no evidence that RPM has adverse outcomes. Further research should focus on developing, implementing, and evaluating an RPM framework., (©Justien Cornelis, Wendy Christiaens, Christophe de Meester, Patriek Mistiaen. Originally published in JMIR Nursing (https://nursing.jmir.org), 19.11.2024.)

COVID-19, caused by SARS-CoV-2 infection, led to a pandemic of acute respiratory illness that is ongoing. High-flow nasal cannula (HFNC) is a commonly used form of respiratory support during acute respiratory distress and is used to treat patients with COVID-19 in many centers. Due to the novel nature of COVID-19 at the onset of the pandemic, evidence to support the use and best practices of HFNC for treating patients with COVID-19 was lacking. This is a review of key peer-reviewed manuscripts from 2022-2023 discussing the efficacy and best practices for using HFNC for patients with COVID-19. Efficacy of HFNC for COVID-19, the use of the respiratory oxygenation index to guide HFNC for COVID-19, and concerns of generated/fugitive aerosols when using HFNC for COVID-19 are emphasized., Competing Interests: Dr Davis is a patent holder of Optate and also a co-founder of both Airbase Breathing Company and Partner Liberia., (Copyright © 2024 by Daedalus Enterprises.)

During the second wave of COVID-19 pandemic, an increasing number of patients experienced breathlessness, which progressed to acute respiratory distress syndrome, leading to the need for supplemental oxygen therapy and mechanical ventilation. With each passing day, the need for medical oxygen increased and simultaneously medical oxygen reserves in the country were getting depleted. Government agencies deployed multipronged strategies to ensure that the hospitals had an adequate supply of medical oxygen. Mechanisms and formulae were devised for the rational allocation of medical oxygen to various regions in the country; the production of medical oxygen was boosted along with the curtailment of oxygen usage in industries; and efficient supply chain management, which included "Oxygen Express"- special trains for transporting oxygen, aircrafts for transporting medical oxygen, creating green corridors and real-time monitoring of oxygen levels using information technology. The usage and promotion of indigenous PSA oxygen technology augmented the medical oxygen generation capacity at the health care facility level. This emergency situation demonstrated a need for strengthening established intersectoral coordination mechanisms for swift and effective responses to similar situations in future. Various strategies adopted by the Central Government and other government agencies to a large extent helped in addressing the medical oxygen emergencies.

Background: COVID-19 is associated with prolonged disability, particularly after critical illness. This study aimed to assess and compare disability post-hospital discharge of subjects who were invasively ventilated versus those who were not, following ICU admission due to COVID-19. This study also explored variables associated with long-term disability., Methods: In this prospective cohort study, subjects with COVID-19 who received invasive ventilation, noninvasive ventilation, or high-flow nasal cannula during ICU stay were assessed with the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 at 3 and 6 months post-hospital discharge. Data were analyzed collectively and stratified as subjects with and without invasive mechanical ventilation. Analysis of variance and multiple regression analyses were applied., Results: The subjects ( N = 43) were mainly male, middle age, and overweight. Subjects who were invasively ventilated ( n = 21) had decreased physical function compared to those who were not during hospital assessments. From 3-6 months after discharge, all WHODAS domains and the overall score decreased in both groups ( P < .001), indicating disability recovery. The participation domain, which assesses joining in society, was the only domain that remained worse in the ventilation group compared to the no ventilation group ( P = .01). No interaction was found between time and the study groups, suggesting that the recovery trajectory was similar. At 6 months, considering the entire cohort, 70% and 56% had no disability in self-care and getting along domains, respectively, while 42% exhibited moderate to severe disability in the participation domain. According to the overall WHODAS score, 86% of subjects still had some level of disability at 6 months. In multivariate analyses, the overall WHODAS score along with the household and participation domains showed significant positive correlations, indicating higher disability, with corticosteroid use., Conclusions: Disability persisted at 6 month post-hospital discharge for ICU survivors of COVID-19, regardless of the need for invasive mechanical ventilation. Participation was the only domain that showed higher disability among those who received invasive ventilation., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

COVID-19 pandemic was accompanied by many healthcare-related issues. Concrete national data regarding the care performance of critical ill cases of COVID-19 does not exist in Korea. The current study aimed to describe the treatment outcome and healthcare resource utilization of critically ill COVID-19 patients. Our multicenter retrospective cohort study enrolled critically ill COVID-19 patients from 22 tertiary care hospitals in Korea. Inclusion criteria: (1) patients aged 19 years or older, (2) patients with laboratory-confirmed SARS-CoV-2 infection who received at least one of following initial treatments such as high-flow oxygen therapy (HFOT) or noninvasive ventilation (NIV) or invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation. During the study wave, a total of 1358 eligible participants were enrolled, with 21 institutions participating in the study. Among them, data from 1113 patients were available and analyzed. Of 921 (82.7%), 621 (55.8%) were supported by IMV. Of the 921 patients supported by HFOT or NIV, 438 (47.6%) recovered without IMV, 429 (46.6%) required IMV, and 54 died who DNR after NIV was applied. Prone position ventilation was administered to 163 (33.1%) patients with IMV and 25 (6.2%) patients with HFOT. Extracorporeal membrane oxygenation was administered to 128 (20.6%) patients treated with IMV. The overall mortality rate was 26.4%. In South Korea, mortality rates for patients with severe COVID-19 pneumonia have been shown substantial fatality, with the highest mortality rates observed in wave 3. The increased mortality rate in wave 3 could be associated with the rapid escalation of critically ill COVID-19 patients and the consequent saturation of intensive care unit capacities. Patients received NIV therapy and prone position ventilation more frequently in wave 3 as the number of cases increased., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The pandemic saw widespread use of home pulse oximeters to patients diagnosed with COVID-19 to support early detection of low oxygen saturation levels and appropriate care. Rapid implementation made conventional evaluation challenging, highlighting the need for rigorous non-randomised methods to support decision-making about future use of these technologies. We used routine data to explore the benefits of pulse oximetry in Greater Manchester, under the 'COVID-19 oximetry at home' (CO@h) programme., Methods: We used data from the Greater Manchester Secure Data Environment and defined study parameters using a 'target trial' model to compare patients receiving pulse oximetry under the CO@h programme, with matched controls using various comparator groups. Primary outcomes were unplanned hospitalisation and all-cause mortality. This study is based on data from the Greater Manchester Care Record (GMCR), using anonymised, routinely collected data provided in a de-identified format for research. Informed written consent is needed for primary care patient data to be collected for service improvement and research, before data extraction to the GMCR. The study was approved under protocol GMCR RQ-048, on 12/05/2022. As indicated by the University of Manchester ethics decision tool, formal ethical approval was not required for this study., Results: The adjusted odds ratios for an unplanned hospitalisation were higher among patients receiving pulse oximetry: OR 1.86 (95% CI 1.54-2.25) at 28 days, 1.5 (95% CI 1.3-1.74) at 90 days and 1.63 (95% CI 1.44-1.83) at 1 year. Overall odds of mortality were lower among patients receiving pulse oximetry: adjusted ORs of 0.5 (95% CI 0.25-0.98) at 28 days, 0.5 (95% CI 0.32-0.78) at 90 days and 0.58 (95% CI 0.44-0.76) at 1 year. The results were robust to different comparison groups., Conclusion: Use of pulse oximetry at home under the CO@h programme, through the resulting prioritisation for appropriate care, was associated with a higher frequency of unplanned admissions and a reduction in the risk of mortality up to 1 year later. Therefore, it is likely effective for early detection of clinical deterioration and timely intervention among patients with COVID-19. Further research is needed to understand whether this is a cost-effective use of healthcare resources., Competing Interests: RW, JD, PB, FR and EK were supported by the NIHR Applied Research Collaboration Greater Manchester (NIHR200174) and RW and JD by the NIHR Manchester Biomedical Research Centre (NIHR203308). As explained in the data availability section, there are restrictions using patient level data and we cannot freely share the data used in this paper through the journal., (Copyright: © 2024 Rubinstein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Post traumatic stress disorder (PTSD) and sleep disorders are prevalent among patients with long COVID. The intersection of PTSD and/or sleep disorders with long COVID is complex. Thus, use of a biopsychosocial lens for assessment and treatment along with a trauma-informed approach to clinical care is recommended. This review provides an overview of the literature on PTSD and sleep disorders among patients with long COVID, including prevalence rates, risk factors, and potential pathophysiology. Pharmacological and non-pharmacological treatment options are reviewed. Also, we provide actionable steps clinicians can integrate into their practice to help effectively assess and treat PTSD and sleep disorders, including validated symptom assessments, recommended referrals, and specific components of non-pharmacological interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lindsey M. Knowles reports financial support was provided by National Institute of Child Health and Human Development. Janna L. Friedly, Jessica A. Bender, Nicole L. Gentile reports financial support was provided by Agency for Healthcare Research and Quality. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cognitive dysfunction is a commonly reported feature of Long COVID (LC). With the overlap of assessment and treatment for cognitive concerns across multiple disciplines, coupled with current guidelines supporting interdisciplinary care, the aim of this clinically focused article is to provide a review of current guidelines and research related to assessment and interventions to address LC-related cognitive concerns within clinical practice from a multidisciplinary perspective, incorporating best practices for collaboration among Clinical Neuropsychologists, Rehabilitation Psychologists, and Speech-Language Pathologists. Current guidelines for assessment and interventions for cognitive functioning are provided, with clinical suggestions for best practices offered. Additional considerations related to diversity and variable patient presentations are identified. This article provides guidance based on current research and practice standards regarding the utilization of a multidisciplinary, collaborative approach to provide comprehensive assessment and treatment for individuals with LC-related cognitive concerns., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sustaining a 'fit-for-purpose' health workforce requires a better understanding of the health care worker cadres that are affected during pandemics and their outcomes. In hospitalized health care workers with confirmed COVID-19 between March 2020 and May 2023 in Liberia, we determined the hospitalization and case fatality rates, type of health care worker cadres affected, their demographic and clinical characteristics and hospital exit outcomes., Methods: This was a cohort study using routine data extracted from hospitalization forms for health care workers in 24 designated COVID-19 treatment facilities., Results: Of the 424 health care workers with COVID-19, hospitalization rates progressively declined between 2020 and 2023, (P<0.001) with the highest rates in 2020 (24/1,000 health care workers) and 2021 (14/1,000 health care workers). Case fatality was 2% in both 2020 and 2021 with no deaths thereafter. Among those hospitalized, the highest proportions were nursing cadres with 191(45%), physicians with 63 (15%) and laboratory technicians with 42 (10%). The most frequent reported site for COVID-19 infection was the health facility (326, 89%). COVID-19 vaccination coverage in health care workers was 20%. The majority (91%) of hospitalizations were for mild symptomatic infections. Even in referral centres (n-52), 18 (35%) were for mild infections. Of the 424 who were hospitalized, 412 (97%) recovered, 9 (2%) died and 3 (1%) either left against medical advice or absconded. Of the nine deaths, none were vaccinated, seven had moderate-to-severe disease but were not referred to specialized COVID-19 treatment centers., Conclusions: The hospitalized health care workers for COVID-19 were predominantly clinical and laboratory personnel who were mostly unvaccinated, and health facilities were hot-spots for contracting infections. The triage and referral system was weak with unnecessary hospitalization of mild infections. This study provides useful insights for outbreak preparedness including priority vaccination and improving health care worker safety in Liberia., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Lehyen DB et al.)

Objective: To compare clinical characteristics and outcomes of hospitalized acute exacerbations of COPD (AECOPD)s secondary to SARS-CoV-2 versus other respiratory viruses amongst a highly vaccinated population in the Omicron era., Design: Retrospective cohort study; analysis of hospital medical records and linked pathology and radiology reports., Setting: Tertiary health network in Victoria, Australia; January 2022-August 2022., Main Outcome Measures: Key clinical information including comorbidities, vaccination status, treatments administered and outcomes such as hospital length of stay, ICU admission, non-invasive ventilation usage and inpatient mortality., Results: One hundred ninety-nine viral AECOPDs - 125 SARS-CoV-2 and 74 other viruses were identified. Of the SARS-CoV-2 group. 13.6% were unvaccinated, 17.6% partially and 68.0% fully vaccinated. The SARS-CoV-2 group were older (77.2 vs 68.9, p < 0.00001) with more comorbidities (1[1-2] vs 1[0-2], p = 0.008) and lower candidacy for full resuscitation (25.6% vs 56.8%, p < 0.0001). Mortality tended to be higher among SARS-CoV2 admission (9.6% v 2.7%, p = 0.066) but rates of ICU admission (10.4% v 13.5%, p = 0.507), length of hospitalisation (5[3-8] vs 5[3-9], p = 0.9) and readmission within 30 days (25% vs 33.3%, p = 0.184) were similar., Conclusion: In a highly vaccinated population in the Omicron era, COPD patients requiring hospitalisation with SARS-CoV-2 are older with more comorbidities than those admitted with other respiratory viruses. Length of hospitalisation and ICU utilisation was similar. Inpatient mortality may be higher., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Chhor et al.)

Long Covid is defined by a wide range of symptoms that persist after the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported symptoms include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other symptoms reported. Symptom range, duration, and severity are highly variable and partially overlap with symptoms of myalgic encephalomyelitis/chronic fatigue syndrome and other post-acute infectious syndromes, highlighting opportunities to define shared mechanisms of pathogenesis. Potential mechanisms of Long Covid are diverse, including persistence of viral reservoirs, dysregulated immune responses, direct viral damage of tissues targeted by SARS-CoV-2, inflammation driven by reactivation of latent viral infections, vascular endothelium activation or dysfunction, and subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, and microbiota dysbiosis. The heterogeneity of symptoms and baseline characteristics of people with Long Covid, as well as the varying states of immunity and therapies given at the time of acute infection, have made etiologies of Long Covid difficult to determine. Here, we examine progress on preclinical models for Long Covid and review progress being made in clinical trials, highlighting the need for large human studies and further development of models to better understand Long Covid. Such studies will inform clinical trials that will define treatments to benefit those living with this condition.

Stress hyperglycaemia is common in critical illness. We have previously observed that increasing severity of respiratory failure in patients with severe COVID-19 is associated with increased insulin demand. Given previously reported direct effects of hypoxia on insulin action, we reasoned that rapid improvements in oxygenation following prone positioning may improve insulin sensitivity and increase risk of hypoglycaemia. A retrospective multi-centre service evaluation comparing blood glucose and insulin administration in patients with COVID-19 pneumonitis receiving prone mechanical ventilation, comparing the 16 h pre-prone and 16 h post-prone time periods. 155 patients were included in this analysis. Oxygenation improved significantly following prone positioning (change in SpO 2 /FIO 2 per hour prone: 3.01 ± 0.14, P < 0.0001). Glycaemic control was similar during the supine and prone study periods, and there were no hypoglycaemic events in the prone study period. Prone positioning was associated with an unexpected modest but significant increase in insulin requirements (mean difference in total insulin dose (IU): 8.32 ± 2.14, P < 0.001) that was robust to several sensitivity analyses, and could not be explained by changes in carbohydrate intake. We did not observe an increased rate of hypoglycaemia during prone ventilation and the adequacy of glycaemic control was comparable during the supine and prone study periods. Unexpectedly, prone ventilation was associated with an increase in insulin requirements despite significant improvement in hypoxaemia. Our findings support the safety of prone ventilation with respect to glycaemic control and identify a novel relationship between ventilation position and insulin requirements in critical illness., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate This study was approved as a multisite service evaluation at the host institution (Cambridge University Hospitals Service development and Audit Department) and participation of additional centres was confirmed with their respective Audit Departments. The study was exempt from the need for NHS research ethics committee review according to UK Health Research Authority guidance, as it was deemed service evaluation using anonymised data. It was reviewed by the institutional review board (Cambridge University Hospitals) and deemed service evaluation using routinely collected data, with no data collected specifically for this study. All data was anonymised by the direct care team before being analysed centrally. The institutional review board confirmed a consent waiver. The study was registered as a multi-site service evaluation at Cambridge University Hospitals (ref number) and at each individual site., (© 2024. The Author(s).)

Background: Low-and middle-income countries (LMICs) face many challenges regarding the timely management of STEMI, and the COVID-19 pandemic has impacted our already fragile health systems., Objectives: To assess the delays in managing STEMI during COVID-19 and evaluate the 6-month mortality rates related to these delays., Methods: A retrospective cross-sectional study was conducted over two years at a tertiary center in Dakar, Senegal. All patients referred for STEMI during the study period were included. Statistical analysis was performed using R, version 4.4.0., Results: During the study period, 273 patients were enrolled (65.9% males, mean age: 59 ± 12.4). Diabetes Mellitus was present in 37.7% of cases. Only 1 out of 5 patients (20.5%) reached medical attention within 1 hour after symptoms onset, and the time from first medical contact to ECG was < 10 minutes in 39 % of cases. Primary PCI within the first 24 hours was performed in 23.5% of cases. Factors significantly associated with late hospital admission (<12h) were first medical contact < 1h (P 0.0009, OR: 4.06 95% CI; 1.8-9.64), time to first ECG < 10 minutes (P 0.002, OR: 2.79 95% CI; 1.45-5.41) and number of facilities visited < 2 (P 0.004, OR: 3.4 95% CI 1.51-8.22). The 6-month mortality rate was 18.7%., Conclusion: Our study found persisting delays in STEMI management in Senegal. Establishing a standard of care for STEMI in Senegal is mandatory to overcome healthcare system weaknesses and improve the outcomes of our STEMI patients., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Background: Severe acute respiratory infection (SARI) is a major cause for hospital admission and associated with high mortality among children worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses and respiratory syncytial virus (RSV) are the most frequently identified pathogens in children with SARI. The duration of care can be affected by the type of infection and patient characteristics. Therefore, the objective of this study was to identify factors affecting the length of hospitalization in children infected with SARS-CoV-2, influenza A and RSV., Methods: We collected data on 713 children with SARI from the medical databases of a university hospital in Hungary. To examine whether there is a difference in the length of hospitalization in children with the SARI Kruskal-Wallis test was performed. To determine the factors that may have an impact on the duration of care a multiple logistic regression analysis was executed., Results: Our results showed that among RSV infected patients the proportions of children requiring intensive care (8.94%), mechanical ventilation (8.94%) and oxygen therapy (13.01%) and suffering from pneumonia (29.27%) were larger than among cases with SARS-CoV-2 and influenza A infection. Considering the age distribution and the duration of care in children with SARI, cases with RSV were significantly younger (p < 0.001) and stayed longer in the hospital (median: 5 days, IQR: 4-7 days, p < 0.001) than those with SARS-CoV-2 and influenza A virus. Multiple logistic regression analysis showed that RSV infection (adjusted odds ratio (aOR): 3.25, 95% confidence interval (CI): 1.43-7.38; p = 0.005), pneumonia (aOR: 3.65, 95% CI: 2.14-6.24; p < 0.001), mechanical ventilation or oxygen therapy (aOR: 3.23, 95% CI: 1.29-8.11; p = 0.012) and underlying illnesses (aOR: 2.39, 95% CI: 1.35-4.23; p = 0.003) significantly increased the odds of hospitalization for more than 4 days., Conclusions: Our research showed that of the viruses causing SARI, RSV had the greatest clinical relevance, contributing to hospital stays of more than 4 days in a large share of paediatric patients below 1 year of age. Our results supply new information on children with SARI, and provide evidence for health policy makers to allocate additional resources to hospitals during SARI epidemics., (© 2024. The Author(s).)

This study investigated the effect of Transcutaneous Electrical Nerve Stimulation (TENS) for fibromyalgia-like symptoms including chronic widespread musculoskeletal pain, fatigue, and/or gait impairment in twenty-five individuals with long-COVID. Participants were randomized to a high dose (intervention group, IG) or low dose (placebo group, PG) TENS device. Both groups received daily 3-5 h of TENS therapy for 4-weeks. The Brief Pain Inventory assessed functional interference from pain (BPI-I), and pain severity (BPI-S). The global fatigue index (GFI) assessed functional interference from fatigue. Wearable technology measured gait parameters during three 30-feet consecutive walking tasks. At 4-weeks, the IG exhibited a greater decrease in BPI-I compared to the PG (mean difference = 2.61, p = 0.008), and improved in gait parameters including stride time (4-8%, test condition dependent), cadence (4-10%, depending on condition), and double-support phase (12% in dual-task) when compared to baseline. A sub-group meeting the 2010 American College of Rheumatology Fibromyalgia diagnostic criteria undergoing high-dose TENS showed GFI improvement at 4-weeks from baseline (mean change = 6.08, p = 0.005). Daily TENS therapy showed potential in reducing functional interference from pain, fatigue, and gait alterations in long-COVID individuals. The study's limited power could affect the confirmation of certain observations. Extending the intervention period may improve treatment effectiveness., (© 2024. The Author(s).)

Patients with both diabetes and coronavirus disease 2019 (COVID-19) are more likely to experience negative outcomes. This study aimed to identify the risk factors associated with these adverse outcomes that can assist clinicians in implementing suitable treatment strategies to minimize the occurrence of severe complications. A total of 92 patients with diabetes and COVID-19 in the Endocrine Department of Zhejiang Provincial Hospital of Chinese Medicine from December 2022 to February 2023 were enrolled and divided into the recovered group and the transfer to the intensive care unit (ICU) or death group. The clinical characteristics and infection indicators were compared between the 2 groups. Additionally, the patients were further divided into the normal group and the reduction group based on their glomerular filtration rate (GFR), and their clinical characteristics and infection indicators were also analyzed. Compared with the GFR normal group, the GFR reduction group exhibited worse outcomes, higher COVID-19 severity, a higher proportion of mechanical ventilation, and a longer hospital stay. However, there were no significant differences in leukocyte, lymphocyte, and neutrophil counts between these 2 groups. Compared with the recovered group, the transfer to ICU or death group demonstrated an increase in leukocytes and neutrophils, while lymphocytes decreased (P < .05). The C-reactive protein, procalcitonin, interleukin-6, and serum amyloid A levels in the transfer to ICU or death group were significantly higher than those in the Recovered group (P < .05). In addition, C-reactive protein, procalcitonin, and serum amyloid A levels in the GFR reduction group were significantly higher than those in the normal group (P < .05), while interleukin-6 levels were only slightly higher (P > .05). In clinical treatment, it is necessary to monitor infection indicators and GFR closely and intervene in time to reduce the occurrence of adverse events., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Post-COVID-19 condition, or syndrome, also known as long COVID, is an infection-associated chronic condition that can develop after a SARS-CoV-2 infection and last at least 3 months to years. Despite representing a high burden for the Unified Health System (SUS), which has affected millions of Brazilians, it has received limited attention in Brazil. Prevalence studies to date have failed to include a broad representation of the population, and there has been insufficient exploration of the impact on people's lives and the burden of and barriers to accessing health services. This article presents the research protocol for the quantitative component of a mixed methods project to produce evidence to inform SUS's provision of care for long COVID. The protocol was designed to study long COVID in SUS patients hospitalised for COVID-19 in a large city in Southeast Brazil to capture symptoms and factors associated with the syndrome, effects on quality of life and employment, health needs, use of health services and barriers to accessing necessary healthcare., Methods and Analysis: An ambidirectional cohort study to capture data retrospectively and prospectively from adults previously discharged from SUS hospitals for COVID-19. The study involves up to two telephone surveys with the patients or proxies selected from a sampling plan for population estimates. Survey questions include baseline and follow-up data on demographic, socioeconomic, comorbidities, work status, health-related quality of life, vaccination status, long COVID symptoms, healthcare needs, use and barriers to access. Descriptive and appropriate multivariable analyses will be employed., Ethics and Dissemination: The project was approved by the Research Ethics Committees of participant institutions and by the Brazilian National Research Ethics Commission. All participants provided verbal consent. We plan to publish articles in scientific journals and multimedia resources for SUS professionals and the general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Increasing evidence has emerged for traditional, complementary and integrative medicine (TCIM) to treat COVID-19 which requires systematic summaries of the net benefits of interventions against standard care and one another. The study aims to conduct a systematic review and network meta-analysis (NMA) regarding TCIM therapies for treating mild/moderate acute COVID-19, potentially informing the WHO guideline development and clinical decision-making., Methods and Analysis: We will search Embase, MEDLINE, Virtual Health Library on Traditional Complementary and Integrative Medicine, Cochrane Central Register of Controlled Trials, WHO's International Clinical Trials Registry Platform with additional searches of Chinese and Korean literature sources for randomised controlled trials comparing TCIM with placebo, standard care, no treatment or with an alternate type of TCIM to treat COVID-19. We will limit the search dates from 2020 to 28 March 2024. Reviewers will, in duplicate, screen eligible articles, extract data and evaluate the risk of bias. We will conduct frequentist network meta-analyses for network comparisons and each outcome. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach and classify interventions from most to least effective or harmful., Ethics and Dissemination: This NMA is based on the existing trials and data which is not subject to ethical approval. We will publish the NMA in a peer-reviewed journal. This may provide methodological reference and clinical evidence for TCIM on future epidemic-prone diseases., Prospero Registration Number: CRD42024517321., Competing Interests: Competing interests: We would like to disclose that Dr. Guyatt Gordon and Dr. Thabane Lehana are listed as members of the Editorial Board of BMJ Open, as noted on their website (https://bmjopen.bmj.com/pages/editorial-board). This association has been declared in accordance with the journal’s submission policies. All other authors have no potential conflicts of interest to declare related to this submission., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chimeric antigen receptor T cell (CAR-T) therapy has emerged as a revolutionary approach in the treatment of malignancies. Despite its remarkable successes, this field continues to grapple with challenges such as scalability, safety concerns, limited therapeutic effect, in vivo persistence, and the need for precise control over CAR expression. In the post-pandemic era of COVID-19 vaccine immunization, the application of messenger RNA (mRNA) encapsulated within lipid nanoparticles (LNPs) has recently garnered significant attention as a potential solution to address these challenges. This review delves into the dynamic landscape of mRNA-LNP technology and its potential implications for CAR-engineered immune cell-based immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Pneumothorax is a little known and reported complication of COVID-19. These patients have poorer general outcomes and greater respiratory support requirements, longer hospitalization times, and higher mortality rates. The purpose of this study was to determine which factors predict mortality in patients with tube thoracostomy diagnosed with COVID-19, admitted to the COVID-19 intensive care unit (ICU), and developing pneumothorax., Methods: This respective, observational study was conducted in all COVID-19 ICUs at the Marmara University Pendik Training and Research Hospital, Türkiye. Patients admitted to the ICU with diagnoses of COVID-19 pneumonia and with chest tubes inserted due to pneumothorax were investigated retrospectively., Results: One hundred patients with tube thoracostomy were included in the study. Their median age was 68 (57-78), and 63% were men. The median follow-up time was 20 [10-29] days, and the median time from initial reverse transcriptase polymerase chain reaction (RT-PCR) results to tube thoracostomy was 17 [9-23] days. Initial RT-PCR results were positive in 90% of the patients, while 8% were negative, and 2% were unknown. Half the patients exhibited pulmonary involvement at thoracic computed tomography (CT) (n = 50), while 22 patients had COVID-19 reporting and data system (CO-RADS) scores of 5 (22%). Sixty-two patients underwent right tube thoracostomy, 24 left side placement, and 14 bilateral placement. The patients' mean positive end expiratory pressure (PEEP) level was 10.31 (4.48) cm H 2 O, with a mean peak inspiratory pressure (PIP) level of 26.69 (5.95) cm H 2 O, a mean fraction of inspired oxygen (FiO2) level of 80.06 (21.11) %, a mean respiratory rate of 23.71 (5.62) breaths/min, and a mean high flow nasal cannula (HFNC) flow rate of 70 (8.17) L/min. Eighty-seven patients were intubated (87%), six used non-rebreathable reservoir masks, four HFNC, two non-invasive mechanical ventilation (NIV), and one a simple face mask. Comorbidity was present in 70 patients, 25 had no comorbidity, and the comorbidity status of five was unknown. Comorbidities included hypertension (38%), diabetes mellitus (23%), cardiovascular disease (12%), chronic obstructive pulmonary disease (5%), malignancy (3%), rheumatological diseases (3%), dementia (2%) and other diseases (9%). Twelve of the 100 patients survived. The median survival time was 20 (17.82-22.18) days, and the median 28-day overall survival rate was 29% (20-38%). The multivariate Cox proportional hazards model indicated that age over 68 (HR = 2.23 [95% CI: 1.39-3.56]; p = 0.001), oxygenation status other than by intubation (HR = 2.24 [95% CI: 1.11-4.52]; p = 0.024), and HCO3- below 22 compared with a normal range of 22 to 26 (HR = 1.95 [95% CI: 1.08-3.50]; p = 0.026) were risk factors associated with mortality in patients in the ICU., Conclusions: Age over 68, receipt of oxygenation other than by intubation, and HCO3- values lower than 22 in patients with COVID-19 pneumonia emerged as prognostic factors associated with mortality in terms of pneumothorax., (© 2024. The Author(s).)

The COVID-19 pandemic has led to an increase in the prevalence of anxiety, stress and depression among affected people. This study was conducted with the aim of investigating the clinical effectiveness of guided breathing exercises in reducing anxiety, stress and depression in patients with COVID-19. A quasi-experimental study design was used, involving a sample of COVID-19 patients who underwent guided breathing exercises as a complementary therapy. After simple sampling, eligible subjects were randomly divided into two groups: intervention (30 patients) and control (30 patients) using random block method. The Depression Anxiety Stress Scale-21 (DASS-21) questionnaire was administered before and after the intervention to evaluate changes in anxiety, stress, and depression levels. The results of this study demonstrated that clinically guided breathing exercises had a significant effect on reducing anxiety and stress in COVID-19 patients. The intervention significantly reduced anxiety and stress scores (p < 0.001). However, there was no significant reduction in depression scores among patients who participated in guided breathing exercises (p = 0.946). Guided breathing exercises are an effective complementary technique in reducing the level of anxiety and stress in COVID-19 patients. Moreover, the exercises may provide a worthy non-pharmacological approach to managing psychological distress in COVID-19 patients., (© 2024. The Author(s).)

Background: Persons with COVID-19 may experience limitations in daily functioning and can be referred to occupational therapy., Objectives: To evaluate changes in daily functioning, cognitive complaints, fatigue and self-management of persons with COVID-19 who received occupational therapy in primary care.To get insights in the volume and duration of occupational therapy., Design: A pre-post observational cohort study from October 2020 until April 2021., Setting: Fifty-eight occupational therapy practices in primary care throughout the Netherlands participated with 68 occupational therapists., Participants: 228 adults (≥18 years) with COVID-19, referred to occupational therapy, gave informed consent and participated in the pre-post evaluation. The mean age was 49 years (SD 13) and 79% of the patients was female. The most frequently reported complaints included fatigue and cognitive complaints., Interventions: Occupational therapy using Dutch guidelines for occupational therapy in clients with COVID-19., Outcome Measures: Performance and satisfaction with performance using the Canadian Occupational Performance Measure (COPM); the impact of Cognitive Complaints on Participation (CoCo-P); and daily activities, self-management and perceived contribution of occupational therapy using the Patient Reported Outcome Measure for Occupational Therapy (PROM-OT)., Results: COPM-performance score improved with a mean difference of 2.9 points (95% CI 2.7 to 3.2), and COPM-satisfaction score improved with 3.2 points (95% CI 2.9 to 3.5). CoCo-P score improved with a mean difference of 20.9 points (95% CI from 14.4 to 27.4), and PROM-OT improved with 42.8 points (95% CI from 40.2 to 45.4). Participants received a median of seven sessions of occupational therapy (IQR 5-10) with a median duration of 18 weeks (IQR 12-25). They valued the contribution of occupational therapy to their improved functioning with a mean score of 8 (SD 1.4) and recommended this to others with a mean score of 9 (SD 1.2)., Conclusions: Persons with COVID-19 who received occupational therapy in primary care improved significantly in daily functioning and highly valued occupational therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Around 463 million people globally have diabetes, of which over 90% have type 2 diabetes (T2D). Projections indicate an expected increase to 700 million by 2045. The COVID-19 pandemic accelerated digital health uptake, establishing virtual consultations as a feasible alternative to traditional in-person care. Despite promising preliminary evidence, a comprehensive review is needed to fully assess the impact of virtual consultations on diabetes care. This review aims to systematically evaluate the impact of remote consultations on the quality of care provided to persons with T2D, by mapping impacts against the six quality domains outlined by the National Academy of Medicine (NAM) (ie, patient-centeredness, effectiveness, efficiency, timeliness, equity and safety)., Methods and Analysis: PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), COCHRANE Library, EMBASE (Excerpta Medica Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Web of Science will be searched for studies published between 2010 and 2024. Primary outcomes will include any quality measures pertaining to the NAM domains for adult patients accessing virtual consultations. The Cochrane Collaboration's tool will be used to assess the quality of the randomised studies, and the Risk of Bias in Non-Randomised Studies of Interventions will be used for non-randomised studies. The findings will be summarised as a narrative synthesis. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews on 15 November 2023 (registration number: CRD42023474219)., Ethics and Dissemination: This review will not include primary data and therefore does not require ethical approval. This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols guidelines. Findings will be disseminated as academic publications and conference presentations and summarised into patient-led lay summaries., Competing Interests: Competing interests: BH works for eConsult Health Ltd, a provider of online consultation platforms for NHS primary, secondary, urgent and emergency care. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Messenger ribonucleic acid (mRNA) therapeutics are attracting attention as promising tools in cancer immunotherapy due to their ability to leverage the in vivo expression of all known protein sequences. Even small amounts of mRNA can have a powerful effect on cancer vaccines by promoting the synthesis of tumor-specific antigens (TSA) or tumor-associated antigens (TAA) by antigen-presenting cells (APC). These antigens are then presented to T cells, eliciting strong antitumor immune stimulation. The potential of mRNA can be further enhanced by expressing immunomodulatory agents, such as cytokines, antibodies, and chimeric antigen receptors (CAR), enhancing tumor immunity. Recent research also explores mRNA-encoded tumor death inducers or tumor microenvironment (TME) modulators. Despite its promise, the clinical translation of mRNA-based anticancer strategies faces challenges, including inefficient targeted delivery in vivo, failure of endosomal escape, and inadequate intracellular mRNA release, resulting in poor transfection efficiencies. Inspired by the approval of lipid nanoparticle-loaded mRNA vaccines against coronavirus disease 2019 (COVID-19) and the encouraging outcomes of mRNA-based cancer therapies in trials, innovative nonviral nanotechnology delivery systems have been engineered. These aim to advance mRNA-based cancer immunotherapies from research to clinical application. This review summarizes recent preclinical and clinical progress in lipid and polymeric nanomedicines for delivering mRNA-encoded antitumor therapeutics, including cytokines and antibody-based immunotherapies, cancer vaccines, and CAR therapies. It also addresses advanced delivery systems for direct oncolysis or TME reprogramming and highlights key challenges in translating these therapies to clinical use, exploring future perspectives, including the role of artificial intelligence and machine learning in their development., (© 2024 The Author(s). WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

Objective: Despite careful design of clinical trials, unforeseen disruptions can arise. The PICOTS (Patient population, Intervention, Comparator, Outcomes, Timepoints, Setting) framework was used to assess disruptions in pain management research imposed by coronavirus disease 2019 (COVID-19) within the Pain Management Collaboratory., Methods: Rapid qualitative methods were employed to identify trial disruptions due to COVID-19 in 11 pragmatic clinical trials of nonpharmacological approaches for pain management. The PICOTS framework was applied by investigators of 4 Collaboratory trials selected to cover 4 types of trial designs (individually randomized, stepped-wedge, cluster, sequential multiple assignment randomized trial-SMART). Interviews with the lead investigators of these trials were completed, and findings were presented/discussed on video calls over a 6-month period (March-August 2021) from which themes/lessons learned were identified and consensus reached., Results: Investigators indicated that patient populations remained generally stable. A major COVID-19 trial disruption was moving from in-person to virtual care affecting delivery of interventions/comparators and outcome assessments. The resultant mixed-mode of care delivery created issues with intervention fidelity posing analytic challenges. COVID-19 also induced ongoing/intermittent delays and other barriers to accessing primary and specialty care at some facilities, creating research capacity issues affecting delivery of experimental interventions requiring sustained, reliable participation of clinical partners. Study designs most affected by COVID-19 were stepped-wedge (intervention/comparator changing over time), cluster (increased site variability inflating intracluster correlation), and SMART (second-stage randomizations disrupted); stratified individually-randomized trials were less vulnerable because of individual-level randomization., Conclusions: PICOTS provides a framework for assessing the impact of trial disruptions in a structured manner. Given the COVID-19 experience, it is important for researchers to consider the potential impact of future trial disruptions during study planning., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the relationship between nutritional scoring systems, nutritional support methods, and the prognosis of severe and critically ill patients infected with the Omicron variant of coronavirus disease 2019 (COVID-19)., Methods: Patients with confirmed Omicron variant severe and critical COVID-19, who were admitted to Chongqing Medical University First Hospital between December 2022 and January 2023, were enrolled into this retrospective study. Clinical data of patients who survived for 28 days were compared with those who died during the same period. Nutritional status was assessed using the 2002 Nutrition Risk Screening (NRS) tool and Prognostic Nutritional Index (PNI). Factors influencing patient mortality were identified by multivariate logistic regression, and the relationship between patient nutrition and mortality as the disease progressed was illustrated using Kaplan-Meier curves. The study was registered on the ChiCTR platform (No. ChiCTR2300067595)., Results: A total of 508 patients were included (349 survivors and 159 non-survivors). Significant differences were found in sex, age, NRS score, PNI score, albumin level, lymphocyte count, chronic comorbidities, mechanical ventilation, neutrophil count, procalcitonin, and platelet count between survivors and non-survivors. Multivariate analysis revealed that high NRS score (OR 3.87, 95% CI, 1.97, 7.63), fourth-level nutritional support (combined enteral and parenteral nutrition; OR 7.89, 95% CI, 1.32, 47.28), chronic comorbidities (OR 4.03, 95% CI, 1.91, 8.51), and mechanical ventilation (OR 6.03, 95% CI, 3, 12.13) were risk factors for mortality (OR > 1). The malnutrition rate among patients with NRS ≥ 3 was 41.93%. The median (interquartile range) PNI score was 38.20 (35.65, 41.25) for survivors versus 32.65 (29.65, 36.58) for non-survivors. The mortality rate was higher in patients with high nutritional risk within 28 days of hospitalization. The descending order for mortality rate in patients receiving different nutritional support was: dual parenteral and enteral nutrition, no nutritional intervention, single enteral nutrition, and single parenteral nutrition., Conclusion: A high proportion of severe and critically ill patients with COVID-19 experience malnutrition, and various factors are associated with their prognosis. High nutritional risk is significantly related to patient mortality. Early assessment using NRS or PNI is crucial for these patients, and personalized interventions should be implemented to improve overall nutritional status, maintain organ function, and enhance the body's antiviral defence., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Objectives: During the course of the coronavirus disease 2019 (COVID-19) pandemic, numerous comorbidities were identified as risk factors for increased morbidity and mortality. Few studies have examined human immunodeficiency virus (HIV) and COVID-19 co-infection and the impact of HIV on COVID-19 outcomes. In this study, we compared outcomes of people living with HIV with COVID-19 with a control group to examine outcomes., Methods: We identified 45 people living with HIV admitted with COVID-19 to one of three large healthcare systems in Memphis, Tennessee, between March 1 and October 31, 2020. We matched the people living with HIV in a 1:1 fashion to a control group of COVID-19-positive patients without a recorded history of HIV and compared clinical outcomes. Nine pairs were not able to be optimally matched, so a sensitivity analysis was completed by repeating the same analyses in the primary analysis while excluding the nine mismatched pairs., Results: Patients did not differ significantly in demographic variables due to the matching algorithm, and there was no significant difference in measured outcomes between people living with HIV and controls. A CD4 count of <200 cells per microliter was not significantly associated with increased morbidity or mortality. Controlling for HIV status, an elevated Charlson Comorbidity Index score of >3 was associated with increased intubation ( P = 0.02), vasopressor use (odds ratio [OR] 4.81, P = 0.04), intensive care unit level of care (OR 4.37, P = 0.007), mortality (OR 7.14, P = 0.02), and length of overall hospital stay in days ( P = 0.004)., Conclusions: We found no difference in outcomes of people living with HIV in comparison to matched controls based on HIV status but found that an increased Charlson Comorbidity Index score led to increased morbidity and mortality regardless of HIV status.

Objective: The study aimed to investigate the impact of COVID-19 on the cascade of HIV care for people living with HIV (PLHIV) in Ethiopia., Design: A retrospective longitudinal study., Setting: The study was conducted in North Showa Zone, Ethiopia, from pre-COVID-19 (January 2018-December 2019) and during COVID-19 (January 2020-December 2021)., Participants: We identified 61901 records from 3925 PLHIV, of which 23 848 were recorded during the pandemic., Main Outcome Measure: We investigated indicators from four stages of the HIV care cascade, including HIV screening and diagnosis, HIV care, HIV treatment and HIV disease progression, according to a WHO framework. The indicator changes were assessed with incidence rate ratios (IRRs)., Results: For HIV screening and diagnosis, the monthly number of HIV tests experienced a 46% decline from 2520 to 1361 since the pandemic (IRR 0.553; 95% CI 0.546 to 0.561). For HIV care, the monthly number of consultations was reduced by 49.6% (from 1582 to 798) since the pandemic (IRR 0.591; 95% CI 0.581 to 0.601). Similarly, the monthly number of viral load tests was reduced by 42.8% (IRR 0.614; 95% CI 0.581 to 0.650). For HIV treatment, the number of antiretroviral therapy (ART) initiations was reduced by 27.8% and the number of ART adherence by 52.5% since the pandemic. For HIV disease progression, the monthly number of PLHIV achieving viral suppression was reduced by 61.6%, while HIV-related deaths doubled during the pandemic., Conclusion: The study highlights pandemic-induced disruptions in the cascade of care for PLHIV. Targeted interventions are necessary to protect PLHIV in public health emergencies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)